[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-433382-105":59,"doc-detail-433382-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","introducing-a-new-hypothesis-in-the-genesis-of-breast-cancer-an-integrative-review-review","Introducing a New Hypothesis in the Genesis of Breast Cancer: An Integrative Review - Review","","Integrative literature review examining a proposed new hypothesis for the genesis of breast cancer, focusing on how hormone exposure relates to tumor development. Article analysis selects relevant studies from 2000–2025 across multiple databases, including PubMed and Cochrane. Findings discuss estrogen–progesterone physiology, combined and isolated hormonal therapy actions, and fibrinolytic physiology, concluding that free estrogen and fibrinogen-related proteins may contribute to immune failure to contain malignant cells.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/introducing-a-new-hypothesis-in-the-genesis-of-breast-cancer-an-integrative-review-review/433382/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/introducing-a-new-hypothesis-in-the-genesis-of-breast-cancer-an-integrative-review-review/433382.png","ImageObject",300,407,{"name":92,"@type":93},"anakgang17","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the objective of this integrative review?","Question",{"text":112,"@type":113},"To introduce a new theory in the medical literature concerning the genesis of breast cancer. It focuses on relationships between hormone exposure and tumor development.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were studies selected for the review?",{"text":117,"@type":113},"The review is based on selected relevant articles published between 2000 and 2025. Sources include Scielo, ScienceDirect, PubMed, Cochrane, and other listed databases.",{"name":119,"@type":110,"acceptedAnswer":120},"What are the main conclusions about estrogen and related proteins?",{"text":121,"@type":113},"Contradictions in existing theories on estrogen’s influence on tumor proliferation lead to new interpretations. The review suggests free estrogen and its by-products related to fibrinogen, including FGL1 and related proteins, may affect immune failure to contain malignant cells.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},433382,1790919857,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41,"preview_page_count":4},962090883568,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Breast Cancer: Targets and Therapy  \nOpen Access Full Text Article REVIEW  \nIntroducing a New Hypothesis in the Genesis of Breast Cancer: An Integrative Review  \nJan Pawel Andrade Pachnicki 1–4 , *, Clara Marie Cayet 1 , *,  \nDiego Akyo Hoshina dos Santos 1 , *, Giovanna Braz Junkes 1 , *, Julia Petry 1 , *, Maria Eduarda Mendes Hibarino 1 , *, Vitória Luisa Lodi Carvalho 1 , *  \n1School of Medicine, Positivo University, Curitiba, Paraná, Brazil; 2School of Medicine, Pontifical Catholic University of Paraná, Curitiba, Paraná, Brazil; 3School of Medicine, Federal University of Paraná, Curitiba, Paraná, Brazil; 4School of Medicine, Mackenzie Evangelical College of Paraná, Curitiba, Paraná, Brazil  \n*These authors contributed equally to this work  \nCorrespondence: Jan Pawel Andrade Pachnicki, School of Medicine, Positivo University, R. Prof. Pedro Viriato Parigot de Souza, 5300, Industrial City, Curitiba, Paraná, 81280-330, Brazil, Tel +55 41 99998-0730, Email [jan.pachnicki@up.edu.br](jan.pachnicki@up.edu.br)  \n| Introduction: Breast cancer is the second most common cancer among women worldwide. Estrogen is currently identified as one of the main agents involved in the initiation of breast tumors; however, evidence indicates a greater risk when estrogen replacement is combined with progesterone, whereas its isolated use does not represent a significant risk. Inconsistencies in existing theories highlight the need for further detailed research on the relationship between hormone exposure and breast tumorigenesis, with particular emphasis on fibrinogen and its components in the context of this review.\u003Cbr>Objective: Introduce a new theory into the medical literature concerning the genesis of breast cancer.\u003Cbr>Methods: This is an integrative literature review based on a selection of relevant articles published between 2000 and 2025, in both Portuguese and English, and sourced from the following databases: Scielo, ScienceDirect, National Library of Medicine, PubMed, Cochrane, Brazilian Journal of Development, and ResearchGate.\u003Cbr>Results: Fifty-six references were selected to support the development of the discussion components, which are subdivided into the following themes: physiology of estrogen and progesterone in the body, actions of hormonal therapies, both combined and isolated, in breast cancer, and fibrinolytic physiology.\u003Cbr>Conclusion: After identifying contradictions in current theories about the influence of estrogen on tumor proliferation, which encouraged the search for new interpretations, it was demonstrated that free estrogen and its by-products, such as fibrinogen-related protein (fibrinogen-like protein 1 and 2), play a role in the immune system’s failure to contain malignant cells, opening another field of therapeutic research for breast cancer.\u003Cbr>Keywords: hormone replacement therapy, estrogen, FGL1, LAG-3, breast cancer, fibrinogen, oncogenesis, crosstalk |\n| --- |\n| Introduction\u003Cbr>Breast cancer represents a major global health burden, according to a study by the International Agency for Research on Cancer (IARC, 2025), an estimated 2.3 million new cases and 670,000 deaths occurred in 2022. The report further indicates that, by 2050, these numbers could rise to 3.2 million new cases and 1.1 million deaths per year, disproportionately affecting countries with a low Human Development Index.1 Given the scale of this challenge, it is important to explore the pathogenesis of the disease, which may involve a complex interplay among genetic alterations, environmental exposures, and dysregulated immune responses, although much remains speculative. Genetic mutations (eg TP53, BRCA1, BRCA2), HER2 amplification, and risk factors such as late menopause or family history are well-established contributors.2 However, HRT and long-term hormonal exposure also represent modifiable elements implicated in breast tumor initiation.3 |\n\nReceived: 2 July 2025  \nAccepted: 3 December 2025  \nPublished: 31 December 2025  \nBreast Cancer:","cbCailuXa1Oxlw2S","https://ap.wps.com/l/cbCailuXa1Oxlw2S","pdf",3666543,12,"English","# Introduction\n# Objective\n# Methods\n# Results\n# Conclusion\n# Keywords","[{\"question\":\"What is the objective of this integrative review?\",\"answer\":\"To introduce a new theory in the medical literature concerning the genesis of breast cancer. It focuses on relationships between hormone exposure and tumor development.\"},{\"question\":\"How were studies selected for the review?\",\"answer\":\"The review is based on selected relevant articles published between 2000 and 2025. Sources include Scielo, ScienceDirect, PubMed, Cochrane, and other listed databases.\"},{\"question\":\"What are the main conclusions about estrogen and related proteins?\",\"answer\":\"Contradictions in existing theories on estrogen’s influence on tumor proliferation lead to new interpretations. The review suggests free estrogen and its by-products related to fibrinogen, including FGL1 and related proteins, may affect immune failure to contain malignant cells.\"}]","Introducing a New Hypothesis in the Genesis of Breast Cancer: An Integrative Review - Review | PDF",1790663876]